Effects of heat stress on mammalian reproduction Hansen, Peter J.
Philosophical transactions of the Royal Society of London. Series B. Biological sciences,
11/2009, Volume:
364, Issue:
1534
Journal Article
Peer reviewed
Open access
Heat stress can have large effects on most aspects of reproductive function in mammals. These include disruptions in spermatogenesis and oocyte development, oocyte maturation, early embryonic ...development, foetal and placental growth and lactation. These deleterious effects of heat stress are the result of either the hyperthermia associated with heat stress or the physiological adjustments made by the heat-stressed animal to regulate body temperature. Many effects of elevated temperature on gametes and the early embryo involve increased production of reactive oxygen species. Genetic adaptation to heat stress is possible both with respect to regulation of body temperature and cellular resistance to elevated temperature.
In cattle, genetic variation exists in regulation of body temperature and stabilization of cellular function during heat stress. There are opportunities to reduce the impact of heat stress on cattle ...production by identifying the causative mutations responsible for genetic variation in thermotolerance and transferring specific alleles that confer thermotolerance to breeds not adapted to hot climates. An example of a mutation conferring superior ability to regulate body temperature is the group of frame-sift mutations in the prolactin receptor gene (PRLR) that lead to a truncated receptor and development of cattle with a short, sleek hair coat. Slick mutations in PRLR have been found in several extant breeds derived from criollo cattle. The slick mutation in Senepol cattle has been introgressed into dairy cattle in Puerto Rico, Florida and New Zealand. An example of a mutation that confers cellular protection against elevated body temperature is a deletion mutation in the promoter region of a heat shock protein 70 gene called HSPA1L. Inheritance of the mutation results in amplification of the transcriptional response of HSPA1L to heat shock and increased cell survival. The case of PRLR provides a promising example of the efficacy of the genetic approach outlined in this paper. Identification of other mutations conferring thermotolerance at the whole-animal or cellular level will lead to additional opportunities for using genetic solutions to reduce the impact of heat stress.
•Genetic variation exists in regulation of body temperature and stabilization of cellular function during heat stress.•There are opportunities to reduce the impact of heat stress on cattle production by transferring specific alleles that confer thermotolerance to breeds not adapted to hot climates.•One successful example of this approach is introgression of the slick mutation in PRLR from Senepol to dairy cattle.
Background: Conflicting findings have been reported on the association between smoking and the risk of venous thromboembolism (VTE).
Objectives: To conduct a prospective, population‐based cohort ...study to investigate the association between cigarette smoking and the risk of incident VTE.
Patients/Methods: Information on smoking habits was assessed by self‐administered questionnaires in 24 576 subjects, aged 25–96 years, participating in the fourth Tromsø Study in 1994–1995. Incident cases of VTE were registered until the end of follow‐up at 1 September 2007.
Results: A total of 389 incident VTE events (1.61 per 1000 person‐years) were registered during follow‐up (median of 12.5 years). Heavy smokers (> 20 pack‐years) had a hazard ratio (HR) of 1.46 (95% confidence interval CI 1.04–2.05) for total VTE, and and an HR of 1.75 (95% CI 1.14–2.69) for provoked VTE, as compared with never smokers. The risk of provoked VTE increased with more pack‐years of smoking (P = 0.02). Smoking was not associated with risk of unprovoked VTE. The number of pack‐years was associated with increased risk of cancer and myocardial infarction, whereas the association between pack‐years of smoking and VTE disappeared when failure times were censored at the occurrence of cancer or myocardial infarction.
Conclusions: Heavy smoking was apparently a risk factor for provoked VTE in analyses with VTE events as the only outcome. The lack of association between smoking and risk of VTE in analyses censored at the occurrence of cancer or myocardial infarction may suggest that smoking‐attributable diseases or other predisposing factors are essential for smoking to convey a risk of VTE.
We report a precision measurement of the parity-violating asymmetry APV in the elastic scattering of longitudinally polarized electrons from 208Pb. We measure APV= 550 ± 16 (stat) ±8 (syst) parts per ...billion, leading to an extraction of the neutral weak form factor FW(Q2= 0.00616 GeV2) = 0.368 ± 0.013. Combined with our previous measurement, the extracted neutron skin thickness is Rn-Rp= 0.283 ± 0.071 fm. The result also yields the first significant direct measurement of the interior weak density of 208Pb: ρ$^0_W$ = -0.0796 ± 0.0036(exp) ± 0.0013(theo) fm-3 leading to the interior baryon density ρ$^0_b$ = 0.1480 ± 0.0036(exp) ± 0.0013(theo) fm-3. Finally, the measurement accurately constrains the density dependence of the symmetry energy of nuclear matter near saturation density, with implications for the size and composition of neutron stars.
•Locked nucleic acid-modified antisense oligonucleotides (LNAs) bind to and modulate RNA.•The high binding affinity of LNAs significantly improves potency.•Structural diversity of LNAs profoundly ...impact many drug properties besides potency.•Harnessing this diversity offers new opportunities for discovering LNA-based drugs.
Over the past 20 years, the field of RNA-targeted therapeutics has advanced based on discoveries of modified oligonucleotide chemistries, and an ever-increasing understanding of how to apply cellular assays to identify oligonucleotides with improved pharmacological properties in vivo. Locked nucleic acid (LNA), which exhibits high binding affinity and potency, is widely used for this purpose. Our understanding of RNA biology has also expanded tremendously, resulting in new approaches to engage RNA as a therapeutic target. Recent observations indicate that each oligonucleotide is a unique entity, and small structural differences between oligonucleotides can often lead to substantial differences in their pharmacological properties. Here, we outline new principles for drug discovery exploiting oligonucleotide diversity to identify rare molecules with unique pharmacological properties.
LNA-modified antisense oligonucleotides (LNAs) are widely used in RNA therapeutics. The structural diversity of LNAs affects most drug properties. Exploiting this diversity offers new opportunities for discovering LNA-based drugs.
Our Milky Way (MW) has witnessed a series of major accretion events in the past. One of the later additions, the
Gaia
-Enceladus merger, has contributed a considerable mass to the inner Galaxy, but ...also generously donated to the outer halo. So far, associations with present-day MW globular clusters (GCs) have been chiefly based on their kinematics and ages. In this work, we present a chemical abundance study of the outer halo (
R
GC
∼ 18 kpc) GC NGC 1261, which has been suggested to be an accreted object based on its younger age. We measured 31 species of 29 elements in two stars from high-resolution
Magellan
/MIKE spectra and find that the cluster is moderately metal poor, at Fe/H = −1.26, with a low scatter of 0.02 dex. NGC 1261 is moderately
α
-enhanced to the 0.3 dex level. While from the small sample alone it is difficult to assert any abundance correlations, the light elements Na, O, Mg, and Al differ significantly between the two stars in contrast to the majority of other elements with smaller scatter; this argues in favor of multiple generations of stars coexisting in this GC. Intriguingly for its metallicity, NGC 1261 shows heavy element abundances that are consistent with
r
-process nucleosynthesis and we discuss their origin in various sites. In particular the Eu overabundance quantitatively suggests that one single
r
-process event, such as a neutron-star neutron-star merger or a rare kind of supernova, can be responsible for the stellar enhancement or even the enrichment of the cluster with the excess
r
material. Its heavy element pattern makes NGC 1261 resemble the moderately enhanced r-I stars that are commonly found in the halo and have been detected in
Gaia
-Enceladus as well. Therefore, combining all kinematical, age, and chemical evidence we conclude that NGC 1261 is a chemically intriguing GC that was born in the
Gaia
-Enceladus galaxy and has been subsequently accreted into the MW halo.
To test the hypothesis that lower extremity progressive resistance training (PRT) can improve muscle strength and functional capacity in patients with multiple sclerosis (MS) and to evaluate whether ...the improvements are maintained after the trial.
The present study was a 2-arm, 12-week, randomized controlled trial including a poststudy follow-up period of 12 weeks. Thirty-eight moderately impaired patients with MS were randomized to a PRT exercise group (n = 19) or a control group (n = 19). The exercise group completed a biweekly 12-week lower extremity PRT program and was afterward encouraged to continue training. After the trial, the control group completed the PRT intervention. Both groups were tested before and after 12 weeks of the trial and at 24 weeks (follow-up), where isometric muscle strength of the knee extensors (KE MVC) and functional capacity (FS; combined score of 4 tests) were evaluated.
KE MVC and FS improved after 12 weeks of PRT in the exercise group (KE MVC: 15.7% 95% confidence interval 4.3-27.0, FS: 21.5% 95% confidence interval 17.0-26.1; p < 0.05), and the improvements were better than in the control group (p < 0.05). The improvements of KE and FS in the exercise group persisted at follow-up after 24 weeks. Also, the exercise effects were reproduced in the control group during the 12-week posttrial PRT period.
Twelve weeks of intense progressive resistance training of the lower extremities leads to improvements of muscle strength and functional capacity in patients with multiple sclerosis, the effects persisting after 12 weeks of self-guided physical activity.
The present study provides level III evidence supporting the hypothesis that lower extremity progressive resistance training can improve muscle strength and functional capacity in patients with multiple sclerosis.
GLOBAL SURFACE TEMPERATURE CHANGE Hansen, J.; Ruedy, R.; Sato, M. ...
Reviews of geophysics (1985),
December 2010, Volume:
48, Issue:
4
Journal Article
Peer reviewed
We update the Goddard Institute for Space Studies (GISS) analysis of global surface temperature change, compare alternative analyses, and address questions about perception and reality of global ...warming. Satellite‐observed night lights are used to identify measurement stations located in extreme darkness and adjust temperature trends of urban and periurban stations for nonclimatic factors, verifying that urban effects on analyzed global change are small. Because the GISS analysis combines available sea surface temperature records with meteorological station measurements, we test alternative choices for the ocean data, showing that global temperature change is sensitive to estimated temperature change in polar regions where observations are limited. We use simple 12 month (and n × 12) running means to improve the information content in our temperature graphs. Contrary to a popular misconception, the rate of warming has not declined. Global temperature is rising as fast in the past decade as in the prior 2 decades, despite year‐to‐year fluctuations associated with the El Niño‐La Niña cycle of tropical ocean temperature. Record high global 12 month running mean temperature for the period with instrumental data was reached in 2010.
Harvesting energy from irregular/random mechanical actions in variable and uncontrollable environments is an effective approach for powering wireless mobile electronics to meet a wide range of ...applications in our daily life. Piezoelectric nanowires are robust and can be stimulated by tiny physical motions/disturbances over a range of frequencies. Here, we demonstrate the first chemical epitaxial growth of PbZr(x)Ti(1-x)O(3) (PZT) nanowire arrays at 230 °C and their application as high-output energy converters. The nanogenerators fabricated using a single array of PZT nanowires produce a peak output voltage of ~0.7 V, current density of 4 μA cm(-2) and an average power density of 2.8 mW cm(-3). The alternating current output of the nanogenerator is rectified, and the harvested energy is stored and later used to light up a commercial laser diode. This work demonstrates the feasibility of using nanogenerators for powering mobile and even personal microelectronics.
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